Improving Tabletability of Excipients by Metal-Organic Framework-Based Cocrystallization: a Study of Mannitol and...

To improve tabletability of pharmaceutical excipient mannitol by forming cocrystal with metal-organic framework (MOF) structure.

Mannitol was cocrystallized with CaCl₂ by slurry method and solvent evaporation method. The obtained cocrystal was characterized by SCXRD, PXRD, and thermal analysis. Comparative study on tabletability between cocrystal and β-mannitol were then conducted. Differences in tabletability were subsequently analyzed using the bonding area-bonding strength (BA-BS) model and correlated with their crystal structures.

The prepared cocrystal contains mannitol, CaCl₂ and water in molar ratio of 1:1:2 (i.e. mannitol·CaCl₂·2H₂O) and all the Ca²⁺ in the cocrystal are linked together by mannitol molecules through an infinite coordination network, demonstrating a typical MOF structure. Compared with β-mannitol, such MOF-based cocrystal showed improved tabletability (~2-fold increased tensile strength) and reduced lamination tendency (~3-fold increased minimum compaction pressure to occur lamination). The tabletability improvement of cocrystal was dominated by its higher BS, which is attributed to stronger intermolecular interactions. The reduced lamination tendency was attributed to its lower in-die elastic recovery than β-mannitol.

MOF-based cocrystallization will be a promising and valuable approach to tailor mechanical properties of pharmaceutical materials in order to achieve better pharmaceutical performance.